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Impaired ex Vivo Leukotriene B₄ Production Characterizes the Metabolic Syndrome and Is Improved after Weight Reduction

University of Western Australia, School of Medicine and Pharmacology, Royal Perth Hospital, Perth, Western Australia 6001, Australia

Address all correspondence and requests for reprints to: Dr. Anne Barden, School of Medicine and Pharmacology, Royal Perth Hospital Unit, P.O. Box X2213, Perth 6847, Australia. E-mail: anne.barden{at}uwa.edu.au.

Context: Neutrophil (polymorphonuclear neutrophil) production of leukotriene B₄ (LTB₄) may be associated with alterations in immune and inflammatory function that characterize the metabolic syndrome (MetS).

Objective: We investigated whether polymorphonuclear neutrophil production of LTB₄ and its metabolites 20-hydroxy-LTB₄ (20-OH-LTB₄) and 20-carboxyl-LTB₄ were altered in subjects with features of the MetS before and after weight reduction.

Design, Setting, Patients, and Intervention: In a case-controlled comparison, men and postmenopausal women with features of the MetS were matched with controls. Subjects with MetS were then matched and randomly assigned to either a 12-wk weight reduction study followed by 4-wk weight stabilization or 16-wk weight maintenance.

Main Outcome Measures: Measurements were performed at baseline and at the end of the 16-wk period. Stimulated neutrophil LTB₄ and its metabolites were measured by HPLC.

Results: In the case-controlled study, body mass index, waist circumference, blood pressure, fasting triglycerides, and glucose were all significantly increased in subjects with features of the MetS (P < 0.05). Production of LTB₄ and 20-OH-LTB₄ was significantly lower compared with controls (P < 0.005). The weight loss intervention resulted in a 4.6-kg reduction in body weight and 6.6-cm decrease in waist circumference relative to controls and a significant increase in LTB₄ and 20-OH-LTB₄.

Conclusions: Subjects with features of the MetS have lower stimulated LTB₄, which is not due to increased metabolism of LTB₄. Weight reduction restored the production of neutrophil LTB₄, suggesting that in addition to modifying cardiovascular risk, weight loss may also help with the management of perturbed inflammatory responses in overweight subjects.